The purpose of this research program is to study roles for serotonin (5-HT) in mouse craniofacial development and to assess the teratogenic potential of serotonergic drugs. We will investigate possible sites of action of 5- HT, its binding protein (serotonin binding protein, SBP) and receptors in epithelial and mesenchyme of the craniofacial region using light and electron microscopic techniques. Direct effects of 5-HT on proliferation, migration and chondrogenic differentiation of neural crest-derived mesenchyme will be studied in cell culture using a variety of cellular and molecular techniques. We will also analyze effects of 5-HT or related drug on cell proliferation in the neuroepithelium of the cranial neural folds, the underlying mesenchyme, and in epithelia of the craniofacial region. Whole embryo culture will be used to determine dose-response relationships and critical periods of exposure for developmental defects produced by 5-HT uptake inhibitors and receptor analogs. These studies will aid in our understanding of the functional importance of 5-HT in morphogenesis generally and will specifically address it role in epithelial-mesenchyme interactions of the developing craniofacial region.